There are a cancer vaccine that prevents virus infection to prevent a cancer caused by a virus, and a cancer vaccine which provides the result that cancer cells are specifically attacked by the immune system via the recognition of a cancer-specific antigen by the immune mechanism, particularly, the cellular immune mechanism in which cytotoxic T cell (CTL) plays an important role. The former is not effective at all for a cancer in which the virus dose not participate. The latter is a cancer therapeutic strategy of targeting an antigen possessed by a cancer cell itself. It is considered that the latter is widely effective for cancers having antigen by specifying the antigen. Inter alia, a cancer vaccine based on the viewpoint of the latter can treat tumors that are difficult to remove by surgical operation because of their size, and causes less side effects as compared with the previous therapies such as chemotherapy and radiation therapy.
WT1 (Wilm's tumor 1) gene is overexpressed in many hematopoietic tumors and solid cancers, for example, acute myelocytic leukemia, acute lymphocytic leukemia, chronic myelocytic leukemia, myelodysplastic syndrome, multiple myeloma, non-Hodgkin's lymphoma, lung cancer, breast cancer, stomach cancer, large intestine/rectum cancer, pancreas cancer, bile duct cancer, head and neck squamous cell cancer, thyroid cancer, kidney cancer, prostate cancer, ovarian cancer, uterine cancer, bone soft tissue sarcoma, malignant melanoma, malignant mesothelioma, testicular germ cell tumor and malignant glioma. Those cancers overproduce the WT1 protein. The WT1 protein is fragmented in a cancer cell to produce partial peptides consisting of 8 to 12 amino acids. A WT1 peptide is one of the peptide fragment which has been bound with the MHC class I molecule in a cancer cell, moved to the surface of the cancer cell, and presented as an antigen bound to the MHC class I molecule on the cancer cell surface. The WT1 peptide becomes a mark of the cancer cell. The amino acid sequence of the WT1 peptide conforms to the type of the MHC class I molecule of the cell. For example, in the case of a cell having HLA-A*0201-type MHC, a HLA-A*0201-type MHC restricted WT1 peptide such as Db126 peptide consisting of 9 amino acids is generated, and in the case of a cell having HLA-A*2402-type MHC, a HLA-A*2402-type MHC restricted WT1 peptide such as Db235 peptide consisting of 9 amino acids is generated. In the case of a cell having other MHC, such as HLA-A26 type (WO2005/095598), HLA-A*3303 type (WO 2007/097358), or HLA-A*1101 type (WO 2008/081701), each MHC restricted WT1 peptide is generated. When a WT1 peptide, or a modified WT1 peptide in which a part of amino acids of the WT1 peptide is substituted or modified is administered to a living body as an antigen (herein, a WT1 peptide or a modified WT1 peptide which has been administered as an antigen is referred to as “WT1 antigen peptide”), the WT1 antigen peptide is bound to the MHC Class I molecule on the surface of a dendritic cell which is an antigen presenting cell, or the WT1 antigen peptide is once taken into a dendritic cell, bound to the MHC class I molecule od the dendritic cell and then, is moved to the surface of the dendritic cell, thereby, is presented as an antigen bound to the MHC class I molecule on the surface of the dendritic cell. An activated dendritic cell having the WT1 antigen peptide/MHC class I molecule complex is moved to the regional lymph node, and activates a CD8-positive T lymphocyte which recognizes the WT1 antigen peptide/MHC class I molecule complex to differentiate and proliferate the cell into a cytotoxic T cell (CTL). CTL recognizes tumor cells having the complex of a WT1 peptide (derived from an endogenous WT1 protein) of the same amino acid sequence as the WT1 antigen peptide and the MHC class I molecule, or a tumor cell having a complex of a WT1 peptide (derived from an endogenous WT1 protein) of an amino acid sequence having cross immunoreactivity with the WT1 antigen peptide and the MHC class I molecule, and attacks the recognized tumor cells. Therefore, the aforementioned various MHC restricted WT1 peptides such as Db126 peptide and Db235 peptide, and modified WT1 peptides in which a part of amino acids of them are substituted or modified are useful as cancer vaccines (Non-Patent Document 1).
It is also known that an adjuvant is utilized in order to enhance the action as cancer vaccine of the WT1 peptide and/or the modified WT1 peptide. As the adjuvant for the WT1 peptide and/or the modified WT1 peptide, for example, mineral gels such as aluminum hydroxide; surfactants such as lysolecithin, and pluronicpolyol; polyanions; peptides; or oil emulsions (Patent Document 1), and GM-CSF, BCG-CWS and Montanide ISA51 (Non-Patent Document 1) are known. In addition to them, a variety of vaccine adjuvants including cyclic dinucleotide analogs (Patent Document 3 and Patent Document 4) such as 1H-imidazo[4,5-c]quinoline-4-amine, imiquimod (Patent Document 2), and cyclic di-GMP (c-di-GMP), and TLR2, 3, 7, 8 and 9 ligands (Patent Document 5) have been known. In addition, it is also known that immunity induced by transdermal administration of imiquimod-containing peptide is further enhanced by adding Peptide-25 (Non-Patent Document 2).
In general, vaccines are administered by subcutaneous or intradermal injection. In addition to those routes, immunity induction by a variety of administration routes, for example, transdermal administration (Patent Document 5 and Non-Patent Document 2), and mucosal administration such as, buccal administration, nasal administration, and sublingual administration (Non-Patent Document 3, Patent Document 6, and Patent Document 7) have been tried.